The Informatics and Statistical Genetics Core (ISGC) of the Program Project Grant (PPG) research will provide novel methodological developments and guidance in a number of areas of relevance to bioinformatics, computational biology, mathematical modeling, data analysis, and population genetics aspects of the PPG. The ISGC researchers will include members of the research teams involved in the 6 applied projects associated with the Consortium as well as additional Consortium members. The specific aims of the ISGC are to: Provide applied bioinformatics and sequence analysis support to he PPG in conjunction with the Molecular Genomics Core (MGC), by overseeing and implementing a variety of operations, e.g., database searches for polymorphism information, flanking sequence identification for genotyping assay development, homology searches for novel sequence findings, evolutionary analysis of sequence information, etc. Provide computational biology support and in silico analysis of polymorphism in the genes chosen for study. These activities include mapping non-synonymous cSNPs onto proteins, where appropriate, and assessing protein interactions via docking experiments, as well as maintaining a WEB site supplying relevant information detailing these activities in order to serve the PPG research broadly. Provide data analysis support and, in particular, novel data analysis methodology development in areas such as haplotype analysis, epistatic interaction analysis, twin analysis, etc. Provide design, oversight, and interpretation of population genetic assays, most notably those used to assess potential genetic stratification and cryptic sample substructure with the study samples. Although we detail activities of the ISGC below, we want to emphasize that some information provided by the ISGC, as well as additional information of relevance to the ISGC, has been integrated into the descriptions of the MGC, the Human Phenotyping/twins Core, the Biochemistry Core, the Administrative Core (AC), as well as the 6 individual research projects. Given page limitations and the nature of the ISGC activities, we have combined the Preliminary Studies and Experimental Design and Methods Sections (sections C and D) and focus on organization in section B, below, and omit sections on Human Subjects, etc. normally at the end of the proposal.